Both of male and female sexual function are similarity includes sexual desire or libido, arousal with penile erection and clitoris engorgement and vaginal lubrication, ejaculation and orgasm phases. Both of male and female sexual dysfunction is a trouble in any one of these function can result from neurogenic disorder, sexual organ vasculargenic disorder, hormongenic disorder and sexual organ pathophysionlogic changes induced by trauma include pubic bone fracture and spinal cord injury and systematic disease such as diabetics or hypertension and taking drugs. Drug induced sexual dysfunction has been proposed as a common pathophysiologic entity and a more than 25% incidence drug-associated sexual dysfunction in a medical outpatient population. Vasodilator, however, have no in relevant to effects on sexual function and even produce an adverse effect on formal sexual function, such as Seagraves et al (Erectile dysfunction associated with pharmacological agents. In: Segraves RT, Schoenberg HW, eds. Diagnosis and Treatment of Erectile Disturbances. New York: Plenum, 1985: 22) and Horowitz and Gobel (Drugs and impaired male sexual function Drugs 18;206, 1979) noted that sexual dysfunction has been associated with virtually every available vasodilator such as antihypertensive agent include that alpha-methyldopa 20-30%, guanethidine 24%, clodidine 41%, reserpine 30-40%, propranolol 13.8%, bendrofluazide 36% of patients and these results indicated that sexual function is special hemodinamic changes in sexual organ and very different from systematic hemodinamic procedure and the most of vasodilator may decrease sexual organ blood perfusion, therefore, induce adverse effects on sexual function.
Clinically sexual dysfunction in male can classify to decreased sexual desire or libido, erectile dysfunction, ejaculatory dysfunction and orgasm disorder, In female also classified to sexual arousal disorder include difficult achieve clitoris engorgement and vaginal lubrication, and orgasm disorder. Frequently, more than one of these problems presents themselves simultaneously.
Sexual dysfunction has been classified to psychogenic disorder and organic disorder. Due to recent progress in diagnostic methods, studies indicated that there are more than 50% of patients found organic disease. According to statistics, it has been reported that the incidences of male and/or female sexual dysfunction was approximately 50% of adults aged 40-70 years old and it is significantly increased by aging.
Traditionally, management of sexual dysfunction based on psychological consultation and tonic drugs and/or tried to use vasodilator attempt to treating sexual dysfunction. However, the succession ratio was very poor. A few of agents which has vasodilating effect such as papaverine, phentolamine and prostaglandine El are only used locally by intra-cavemosal injection therapy clinically. However, these agents are restrictedly used because of frequency of undesirable side effects including lowering systematic blood press, pain, prolonged erection such as priapism and penile fibrosis, and it is difficult used as an oral administration.
Recently, scientists demonstrate the detailed special structure of sexual organ of corpus cavernosum(CC) in male and clitoris in female, which is like a closed cylinder surrounded by outline with connective tissue membrane tunica albuginea and the inside contains special erectile tissue CC which consist of special smooth muscle, collagen and elastin, and linked by associate arteries, veins and nerves. The mechanism of regulation smooth muscle tone in CC is very different from systematic blood vessels, and there are specially distributed non-adrenalin non-cholinergic (NANC) nerve terminal which synthesis and release nitric oxide(NO) and phosphodiesterase type V(PDE5) which specially distributed in sexual organ plays the most important role in regulation of sexual function.
Sexual activity is a special hemodynamic procedure in sexual organ which mediated by relaxation of CC smooth muscle and its associated arterioles to increase blood flow into CC and reduce vein leakage to induce penile erection or clitoris engorgement. Such a sexual function is mediated by neuro-endocrinery regulation. During sexual stimulation, non-adrenalergic non cholenergic(NANC) nerve terminal which is specially distributed on CC, synthesis and release nitric oxide(NO) by NO synthesis(NOS), NO increased cGMP levels induce relaxation smooth muscle of CC and associate arteries, increase CC blood flow to induce penile erection or clitoris engorgement. cGMP which is the most important molecular can hydrolytic breakdown by cGMP specific phosphodiesterase V(PDE5) and loss its activity. So, NO-cGMP signaling pathway plays the important key role in regulation of sexual function. This important discovery in molecular biological researches demonstrated that among of the molecular which plays the most important role of regulating sexual function are included nitric oxide(NO), nitric oxide synthssis(NOS), gunylate cyclase(GC) and CGMP and PDE5. Agent, therefore, which has specific inhibiting effect on PDE5 activity to increase CC cGMP levels can be used for oral medication to treatment of sexual dysfunction with or without systematic side effects.
Recent study demonstrated that PDE5 is specifically distributed in CC compared to systematic blood vessels and other organs(the ratio is more than 10000 times) and PDE5 specific inhibitor such as Sildenafil can block cGMP hydrolysis to increase cGMP levels for using oral medication for treating sexual dysfunction in clinically. Sildenafil however, merely induces a transient erection by using a chemical agent, are too expensive and may cause undesirable systematic side effects including flashing, headache, cardiac problem and visional problem. Therefore, uses such a transient therapy is also restricted clinically.
Ideal drug for treating sexual dysfunction should be as an oral administration and have the specific action on sexual organ to enhancing sexual activity and safe and no or minimal of systematic side effects and have the long-term therapeutic activity. Recent studies have taken a growing interest in search a therapeutic agent for sexual dysfunction more focus on NO-cGMP specific PDE5 inhibitor for specific action on sexual organ to reduce systematic side effects.
Icariin is isolated from natural plant Epimedii herba, which is as a standard compound used for drug analysis only by now, a few studies reports the effects of icariin on enhancing immunomodulating effect, anti-hepatotoxic, anti-fatigue, prevention of aging and mild vasodilating activities. However, no any effects of icariin for enhancing sexual function has been reported.